Proteolysis and the cell cycle: with this RING I do thee destroy

The ubiquitin system drives the cell division cycle by the timely destructi on of numerous regulatory proteins. Remarkably, the two main activities tha t catalyze substrate ubiquitination in the cell cycle, the Skp1-Cdc53/culli n-F-box protein (SCF) complexes and the anaphase-promoting complex/cyclosom e (APC/C), define a new superfamily of E3 ubiquitin ligases, all based on r elated cullin and RING-H2 finger protein subunits. The circuits that interc onnect the SCF, APC/C and cyclin-dependent kinase activities form a master oscillator that coordinates the replication and segregation of the genome.